JFK screwed up in the Bay of Pigs. While he publicly accepted "full responsibility," he said privately (meaning: leaked to trusted reporters, off the record) that he wanted to "smash the CIA," thereby putting the blame on them. He eventually got rid of Allan Dulles and Richard Bissell, the architects of the Bay of Pigs, and appointed his own man, John McCone as Director of Central Intelligence. The CIA redeemed itself in JFK's esteem during the missile crisis. The CIA had no motivation to kill JFK.

The Mafia and Castro had motivation to kill JFK. But, while those and other conspiracy theories are good on motivation, they fall down when you start probing for details. The only thing I'm certain of is that we will never know what really happened, and why.